Inhibitory Effect of Green Tea Polyphenols on Membrane-Type 1 Matrix Metalloproteinase, MT1-MMP1

Matrix metalloproteinases (MMPS), especially membrane-type 1 matrix metalloproteinase (MT1-MMP), which generates an active form of MMP-2 from proMMP-2, are deeply involved in angiogenesis as well as in tumor cell migration and metastasis. To obtain a specific inhibitor for MT1-MMP, we screened a num...

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Published inBiological & Pharmaceutical Bulletin Vol. 26; no. 9; pp. 1235 - 1238
Main Authors Oku, Naoto, Matsukawa, Motomi, Yamakawa, Satoru, Asai, Tomohiro, Yahara, Shoji, Hashimoto, Fumio, Akizawa, Toshifumi
Format Journal Article
LanguageJapanese
English
Published Pharmaceutical Society of Japan 2003
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Abstract Matrix metalloproteinases (MMPS), especially membrane-type 1 matrix metalloproteinase (MT1-MMP), which generates an active form of MMP-2 from proMMP-2, are deeply involved in angiogenesis as well as in tumor cell migration and metastasis. To obtain a specific inhibitor for MT1-MMP, we screened a number of natural and synthetic compounds using recombinant human MMP-2, MMP-7, and soluble MT1-MMP in a fluorogenic peptide cleavage assay (-)-Epigallocatechin 3-O-gallate (EGCG) followed by (-)-epigallocatechin 3, 5-di-O-gallate and epitheaflagallin 3-0-gallate, was found to have potent and distinct inhibitory activity against MT1-MMP. Therefore, we investigated the effect of EGCG on the suppression of MMP-2 activation as determined by gelatin zymography, and observed that the active form of MMP-2 in the conditioned medium of human umbilical vein endothelial cells was decreased in the presence of EGCG. The results suggest the possibility that tea polyphenols suppress tumor growth through the suppression of angiogenesis.
AbstractList Matrix metalloproteinases (MMPS), especially membrane-type 1 matrix metalloproteinase (MT1-MMP), which generates an active form of MMP-2 from proMMP-2, are deeply involved in angiogenesis as well as in tumor cell migration and metastasis. To obtain a specific inhibitor for MT1-MMP, we screened a number of natural and synthetic compounds using recombinant human MMP-2, MMP-7, and soluble MT1-MMP in a fluorogenic peptide cleavage assay (-)-Epigallocatechin 3-O-gallate (EGCG) followed by (-)-epigallocatechin 3, 5-di-O-gallate and epitheaflagallin 3-0-gallate, was found to have potent and distinct inhibitory activity against MT1-MMP. Therefore, we investigated the effect of EGCG on the suppression of MMP-2 activation as determined by gelatin zymography, and observed that the active form of MMP-2 in the conditioned medium of human umbilical vein endothelial cells was decreased in the presence of EGCG. The results suggest the possibility that tea polyphenols suppress tumor growth through the suppression of angiogenesis.
Author Toshifumi AKIZAWAb
Motomi MATSUKAWAb
Naoto OKUa
Shoji YAHARAc
Fumio HASHIMOTOd
Tomohiro ASAIa
Satoru YAMAKAWAa
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Setsunan University
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